Our previous study demonstrated that a cis-acting element for neuron-specific splicing of human amyloid precursor protein (APP) gene existed in an intron region flanking to exon 8. In this study, we extended the analysis by deletion and mutagenesis experiments and identified two distinct cis-acting elements which modulate the splicing of exon 8 of the APP gene in a sequence-dependent manner. Both elements are located at the just upstream region of the so-called branchpoint sequence, the first (ATGTTT) at -42 to -47 nt and the second (TTT) at -36 to -38 nt upstream from exon 8. Our study suggested that the first one is a positive element for the splicing of exon 8 and the second a negative one for the splicing.
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